In this Program Project renewal application, we will continue to investigate the structural and dynamic aspects of DNA as they relate to biological recognition. The Core Facility will continue to provide members of the Project with DNA samples (including isotopically labelled DNA) and to maintain a state-of- the-art NMR and data processing facility. The variation of DNA structure as a function of sequence will be studied in several biologically important DNA sequences by a variety of techniques, including distance geometry methods. The sequences to be studied include restriction endonuclease sites, promoters, enhancer sites, and operator DNAs. The dynamic behavior of DNA will be studied across several timescales using high-resolution NMR, solid-state deuterium NMR, ESR and optical relaxation methods. Sequence-specific complexes of DNA with drugs and repressor proteins will be studied by optical methods and by high- resolution NMR methods, including heteronuclear NMR.